Precision-T: A Randomized Study of Orca-T in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

NCT05316701 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: Precision-T (PhIII component)
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 19

Brief Summary

This study will evaluate the safety, tolerability, and efficacy of Orca-T, an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons) in participants undergoing myeloablative allogeneic hematopoietic cell transplant transplantation for hematologic malignancies. This posting represents the Phase III component of Precision-T. The Precision-T Ph1b component is described under NCT04013685.

Conditions

Undifferentiated Leukemia; Myelodysplastic Syndrome; Acute Leukemia; Therapy-Related Myelodysplastic Syndrome; Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Mixed Phenotype Acute Leukemia

Keywords

hematopoietic stem cell transplantation; acute leukemia; Myelodysplastic syndromes; matched related donor; matched unrelated donor; myelodysplastic syndrome

Outcome Measures

Primary Outcomes (1)

• Event-free at 12 Months for Moderate or Severe Chronic Graft-versus-Host-Disease-free Survival (cGFS) Per Endpoint Adjudication Committee (EAC)

  Event-free rate estimated at 12 months for cGFS per EAC, which is defined as the time from date of allogeneic hematopoietic cell transplantation (alloHCT) (ie, day 0) to date of death from any cause or first onset of moderate or severe chronic graft-versus-host disease (cGVHD) (graded per NIH consensus criteria), whichever was earliest, within 2 years after day 0. cGVHD was assessed and graded by EAC blinded to treatment assignment. Each participant in the study is followed for up to 730 days after transplant. Primary analysis was event driven (ie, when 56 participants had died or had moderate or severe cGVHD) and was not based on duration of follow-up. The analysis was conducted using all available data at the time that the 56th event occurred, and event-free rate at 12 months was estimated regardless of length of follow-up for individual participants. At the time of analysis, not all participants have reached 730 days of follow-up because they enrolled at different times.

  Day 0 through 730 days after transplantation

Secondary Outcomes (3)

• Event Rate at 12 Months for Time to Moderate or Severe cGVHD Per EAC

  Day 0 through 730 days after transplantation

• Event-free at 12 Months for Overall Survival (OS)

  Up to 730 days after end of enrollment

• Event-free Rate at 12 Months for Graft-versus-host Disease-free and Relapse-free Survival (GRFS) Per EAC

  Day 0 through 730 days after transplantation

Study Arms (2)

Orca-T

EXPERIMENTAL

For patients randomized to the Orca-T arm, Orca-T will be administered after myeloablative conditioning regimen. Single-agent GVHD prophylaxis with tacrolimus will be administered following Tcon infusion (generally Day +3).

Biological: Orca-T

Standard of Care alloHCT Control

ACTIVE COMPARATOR

For patients randomized to the standard-of-care control arm, an unmanipulated allograft derived from the peripheral blood of a matched donor will be administered after a myeloablative conditioning regimen. Dual-agent prophylaxis consisting of tacrolimus plus methotrexate will be administered starting on Day -3.

Biological: Standard-of-Care

Interventions

Standard-of-Care BIOLOGICAL

unmanipulated donor allograft

Also known as: SOC

Standard of Care alloHCT Control

Orca-T BIOLOGICAL

an allogeneic stem cell and T-cell immunotherapy biologic

Orca-T

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Matched to a related or unrelated donor who is an 8/8 match for HLA-A, -B, -C, and DRB1
• Diagnosed with one of the following diseases:
• Acute myeloid, lymphoid or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi), with or without the presence of known minimal residual disease
• Myelodysplastic syndromes (MDS) that are indicated for alloHSCT per 2017 International Expert Panel recommendations and/or have therapy-related/secondary MDS, with ≤ 10% blast burden in the bone marrow
• Planned to undergo MA-alloHCT including one of the following myeloablative conditioning regimens:
• TBI/Cy
• TBI/Etoposide
• BFT
• Cardiac ejection fraction at rest ≥ 45% or shortening fraction of ≥ 27% by echocardiogram or radionuclide scan (MUGA)
• Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%
• Negative serum or urine beta-HCG test in females of childbearing potential
• ALT/AST \< 3 times ULN
• Recipients in screening must screen negative for SARS-CoV-2 RNA using a PCR-based test
• Disease Risk Index (DRI) overall risk categorization of intermediate or high
• Total bilirubin ≤ upper limit of normal (ULN)

You may not qualify if:

• Prior allogeneic HCT
• Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
• Planned donor lymphocyte infusion (DLI)
• Planned pharmaceutical in vivo or ex vivo T cell depletion
• Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor
• Karnofsky performance score \< 70%
• Hematopoietic cell transplantation-specific Comorbidity Index (HCT-CI) \> 4
• Uncontrolled bacterial, viral or fungal infections at time of enrollment
• Seropositive for HIV-1 or -2, HTLV-1 or -2, Hepatitis B sAg, Hepatitis C antibody
• Known allergy or hypersensitivity to, or intolerance of, tacrolimus
• Documented allergy or hypersensitivity to iron dextran or bovine, murine, algal or Streptomyces avidinii proteins
• Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
• Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected
• Psychosocial circumstances that preclude the patient being able to go through transplant or participate responsibly in follow up care
• Women who are pregnant or breastfeeding

Sponsors & Collaborators

• Orca Biosystems, Inc.: lead

Study Sites (19)

City of Hope

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Davis

Sacramento, California, 95817, United States

Location

Stanford Health Care

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute - Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System - Michigan Medicine

Ann Arbor, Michigan, 48109, United States

Location

Weill Cornell Medicine - New York-Presbyterian Hospital

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Sciences University - Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37239, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Meyer EH, Salhotra A, Gandhi AP, Pantin J, Patel SS, Hoeg RT, Gomez-Arteaga A, Faramand R, Tamari R, Waller EK, Kosuri S, Jimenez Jimenez AM, Holter-Chakrabarty J, Dholaria B, Chen YB, Hamilton BK, Magenau J, Eghtedar A, Murray JM, Pavlova A, Fernhoff NB, McClellan JS, Killian MS, Li A, Negrin RS, Oliai C. Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial. Blood. 2026 Mar 12;147(11):1168-1177. doi: 10.1182/blood.2025031313.

  PMID: 41385341 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Orca Biosystems, Inc.

info@orcabio.com

530-414-9743

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Phase III is a randomized, open-label, multicenter study comparing outcomes between patients receiving Orca-T followed by single-agent tacrolimus or standard-of-care (SOC) control followed by dual agent, tacrolimus-based Graft-versus-Host-Disease (GVHD) prophylaxis regimen

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: April 7, 2022
• Study Start: June 21, 2022
• Primary Completion: July 15, 2024
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 4, 2026
• Results First Posted: September 26, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)